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用于个性化治疗的非动物胶质母细胞瘤模型

Non-animal glioblastoma models for personalized treatment.

作者信息

Zottel Alja, Jovčevska Ivana, Šamec Neja

机构信息

Centre for Functional Genomics and Bio-Chips, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Zaloška cesta 4, 1000, Ljubljana, Slovenia.

出版信息

Heliyon. 2023 Oct 16;9(10):e21070. doi: 10.1016/j.heliyon.2023.e21070. eCollection 2023 Oct.

DOI:10.1016/j.heliyon.2023.e21070
PMID:37928397
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10622609/
Abstract

Glioblastoma is an extremely lethal cancer characterized by great heterogeneity at different molecular and cellular levels. As a result, treatment options have moved far from systemic and universal therapies toward targeted treatments and personalized medicine. However, for successful translation from preclinical studies to clinical trials, experiments must be performed on reliable disease models. Numerous experimental models have been developed for glioblastoma, ranging from simple 2D cell cultures to study the nature of the disease to complex 3D models such as neurospheres, organoids, tissue-slice cultures, bioprinted models, and tumor on chip, as perfect prototypes to evaluate the therapeutic potential of different drugs. The presence of multiple research models is consistent with the complexity and molecular diversity of glioblastoma. The advantage of such models is the recapitulation of the tumor environment, and in some cases the preservation of immune system components as well as the creation of simple vessels. There are also two case studies translating studies on glioblastoma organoids to patients as well as four ongoing clinical trials using glioblastoma models, indicating high clinical potential of glioblastoma models.

摘要

胶质母细胞瘤是一种极具致死性的癌症,其特点是在不同分子和细胞水平上具有高度异质性。因此,治疗方案已从全身性和普遍性疗法转向靶向治疗和个性化医疗。然而,为了成功地将临床前研究转化为临床试验,必须在可靠的疾病模型上进行实验。针对胶质母细胞瘤已开发出众多实验模型,从用于研究疾病本质的简单二维细胞培养到复杂的三维模型,如神经球、类器官、组织切片培养、生物打印模型和芯片上肿瘤等,这些都是评估不同药物治疗潜力的完美原型。多种研究模型的存在与胶质母细胞瘤的复杂性和分子多样性相一致。此类模型的优势在于能够重现肿瘤环境,在某些情况下还能保留免疫系统成分以及创建简单血管。此外,还有两项将胶质母细胞瘤类器官研究转化应用于患者的案例研究,以及四项正在进行的使用胶质母细胞瘤模型的临床试验,这表明胶质母细胞瘤模型具有很高的临床潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d5/10622609/cf75a85991a8/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d5/10622609/140a260084dd/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d5/10622609/cf75a85991a8/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d5/10622609/140a260084dd/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d5/10622609/cf75a85991a8/gr2.jpg

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FDA no longer has to require animal testing for new drugs.美国食品药品监督管理局不再需要对新药进行动物试验。
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Recent advances in organotypic tissue slice cultures for anticancer drug development.近年来,器官型组织切片培养在抗癌药物研发方面取得了进展。
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Glioblastoma, from disease understanding towards optimal cell-based in vitro models.胶质母细胞瘤:从疾病认识到最佳的基于细胞的体外模型。
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Patient-Derived Tumor Organoids for Guidance of Personalized Drug Therapies in Recurrent Glioblastoma.患者来源的肿瘤类器官用于指导复发性胶质母细胞瘤的个体化药物治疗。
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Comparative single-cell RNA-sequencing profiling of BMP4-treated primary glioma cultures reveals therapeutic markers.比较 BMP4 处理的原发性神经胶质瘤培养物的单细胞 RNA 测序分析揭示了治疗标志物。
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Antitumor Activity of a Mitochondrial-Targeted HSP90 Inhibitor in Gliomas.线粒体靶向 HSP90 抑制剂在脑胶质瘤中的抗肿瘤活性。
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Cancer cell heterogeneity and plasticity: A paradigm shift in glioblastoma.肿瘤细胞异质性和可塑性:胶质母细胞瘤的范式转变。
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